3-39143567-G-A

Variant names:

• chr3-39143567-G-A
• NM_033027.4:c.1258C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033027.4(CSRNP1):​c.1258C>T​(p.Leu420Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: CSRNP1 NM_033027.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72

Genes affected

CSRNP1 (HGNC:14300): (cysteine and serine rich nuclear protein 1) This gene encodes a protein that localizes to the nucleus and expression of this gene is induced in response to elevated levels of axin. The Wnt signalling pathway, which is negatively regulated by axin, is important in axis formation in early development and impaired regulation of this signalling pathway is often involved in tumors. A decreased level of expression of this gene in tumors compared to the level of expression in their corresponding normal tissues suggests that this gene product has a tumor suppressor function. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08970079).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSRNP1	NM_033027.4	c.1258C>T	p.Leu420Phe	missense_variant	Exon 5 of 5	ENST00000273153.10	NP_149016.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSRNP1	ENST00000273153.10	c.1258C>T	p.Leu420Phe	missense_variant	Exon 5 of 5	1	NM_033027.4	ENSP00000273153.5
CSRNP1	ENST00000514182.1	c.1258C>T	p.Leu420Phe	missense_variant	Exon 5 of 5	1		ENSP00000422532.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 74

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1258C>T (p.L420F) alteration is located in exon 5 (coding exon 4) of the CSRNP1 gene. This alteration results from a C to T substitution at nucleotide position 1258, causing the leucine (L) at amino acid position 420 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.090	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.71	N;N
REVEL	Benign	0.031
Sift	Benign	0.16	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.10	B;B
Vest4		0.20
MutPred		0.28		Loss of stability (P = 0.1737);Loss of stability (P = 0.1737);
MVP		0.21
MPC		0.36
ClinPred		0.14	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.047
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-39185058;